Improved recombinant retroviral titers utilizing trichostatin A

Recombinant retroviruses are a common vehicle to deliver an exogenous gene to a target cell, which makes them a useful tool in the field of gene thera py. A major drawback to using recombinant retroviruses is the low titer ach ieved, resulting in a limited number of target cells infected and subsequen tly poor expression of a transgene. In this study, we created art ecotropic producer cell line that contained recombinant mouse nerve growth factor (N GF) and the reporter gene LacZ. This cell line, termed psi(2)/LIG/NGF; was treated with the drug trichostatin A, an inhibitor of histone deacetylase. At a concentration of 3 mu M trichostatin A, the retroviral titer of this p roducer cell line was increased 34-fold relative to untreated control cells and 3.4-fold compared to the commonly used hyperacetylating compound sodiu m butyrate. Producer cells treated with trichostatin A also increased the n umber of primary rat marrow stromal cells infected 5.8-fold compared to unt reated producer cells. These results offer a simple and effective solution for converting low titer producer cell clones to higher titer clones, which can be easily tested and applied.